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000169159 1001_ $$aZiegler, Berenice$$b0
000169159 245__ $$aThe Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra.
000169159 260__ $$aHeidelberg$$bSpringer$$c2021
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000169159 520__ $$aThe Hydra head organizer acts as a signaling center that initiates and maintains the primary body axis in steady state polyps and during budding or regeneration. Wnt/beta-Catenin signaling functions as a primary cue controlling this process, but how Wnt ligand activity is locally restricted at the protein level is poorly understood. Here we report a proteomic analysis of Hydra head tissue leading to the identification of an astacin family proteinase as a Wnt processing factor.Hydra astacin-7 (HAS-7) is expressed from gland cells as an apical-distal gradient in the body column, peaking close beneath the tentacle zone. HAS-7 siRNA knockdown abrogates HyWnt3 proteolysis in the head tissue and induces a robust double axis phenotype, which is rescued by simultaneous HyWnt3 knockdown. Accordingly, double axes are also observed in conditions of increased Wnt activity as in transgenic actin::HyWnt3 and HyDkk1/2/4 siRNA treated animals. HyWnt3-induced double axes in Xenopus embryos could be rescued by coinjection of HAS-7 mRNA. Mathematical modelling combined with experimental promotor analysis indicate an indirect regulation of HAS-7 by beta-Catenin, expanding the classical Turing-type activator-inhibitor model.We show the astacin family protease HAS-7 maintains a single head organizer through proteolysis of HyWnt3. Our data suggest a negative regulatory function of Wnt processing astacin proteinases in the global patterning of the oral-aboral axis in Hydra.
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000169159 650_7 $$2Other$$aAstacin
000169159 650_7 $$2Other$$aAxis formation
000169159 650_7 $$2Other$$aHydra
000169159 650_7 $$2Other$$aProteinase
000169159 650_7 $$2Other$$aWnt signaling
000169159 7001_ $$aYiallouros, Irene$$b1
000169159 7001_ $$aTrageser, Benjamin$$b2
000169159 7001_ $$aKumar, Sumit$$b3
000169159 7001_ $$aMercker, Moritz$$b4
000169159 7001_ $$aKling, Svenja$$b5
000169159 7001_ $$aFath, Maike$$b6
000169159 7001_ $$0P:(DE-He78)7b85969869bce221ac5186173255845f$$aWarnken, Uwe$$b7$$udkfz
000169159 7001_ $$0P:(DE-He78)38b33779833838a98c2a241ce465fb07$$aSchnölzer, Martina$$b8$$udkfz
000169159 7001_ $$aHolstein, Thomas W$$b9
000169159 7001_ $$aHartl, Markus$$b10
000169159 7001_ $$aMarciniak-Czochra, Anna$$b11
000169159 7001_ $$aStetefeld, Jörg$$b12
000169159 7001_ $$aStöcker, Walter$$b13
000169159 7001_ $$00000-0003-2569-3942$$aÖzbek, Suat$$b14
000169159 773__ $$0PERI:(DE-600)2133020-7$$a10.1186/s12915-021-01046-9$$gVol. 19, no. 1, p. 120$$n1$$p120$$tBMC biology$$v19$$x1741-7007$$y2021
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